Kidney Transplantation From Old Deceased Donors: Impact of Uric Acid Level-A Quarter-Century of Experience in One Transplant Center.

BACKGROUND: The long-term burden of higher donor age on graft function and survival after kidney transplantation remains uncertain. Because both recipient and donor characteristics have evolved and the general population age is on the increase, we looked at the causes of kidney graft outcome. AIM: The aim of this study was to evaluate the impact of different clinical parameters on long-term outcome of older-donor kidney transplantation. This retrospective study included 345 adult patients (58 patients received kidney from donors at least 55 years old) transplanted between January 1993 and December 2005 and were followed in one center throughout the post-transplant course (median, 9.4 years). Data included recipient and donor age, cold ischemia time, delayed graft function, panel reactive antibodies, HLA mismatch, time on dialysis, graft function at different time points, uric acid level, proteinuria, immunosuppression, and biopsy-proven rejection. RESULTS: Improvement of estimated glomerular filtration rate at 36 months after transplantation was a good prognostic factor for long-term kidney function. Higher donor age decreased the chance for improvement of kidney function by 2.8% per year of life (P = .0244). Hyperuricemia was found in 46% of the study population; estimated glomerular filtration rate less than 50 mL/min/1.72 m2 was associated with hyperuricaemia. A higher uric acid level was associated with inferior kidney function in recipient of older kidneys. Graft failure occurred late (median, 6.3 years post-transplantation) in 26 (44.8%) of older-donor recipients and in 87 (30.3%) of the remaining patients. CONCLUSIONS: Our results suggest an important association between older donor age and decreased allograft function in kidney recipients with elevated uric acid level. Recipients of older kidneys with normal uric acid level presented satisfactory outcomes.

Expression of PBMC TLR4 in Renal Graft Recipients Who Experienced Delayed Graft Function Reflects Dynamic Balance Between Blood and Tissue Compartments and Helps Select a Problematic Patient.

Both Toll-like receptor 4 (TLR4) and monocytes focus stimuli, causing them to contribute differently to chronic injury of a transplanted kidney. AIM: The aim of our study was to determine if TLR4 monocyte is a diagnostic tool and possibly a target for therapeutic intervention. MATERIALS: We studied 143 kidney transplant (KT) patients (88 male, 55 female; 50.3 ± 12.8 years); median was 10.4 post KT, follow-up was 11.4 months, and 46 patients had delayed graft function (DGF+) history. Control group (38 healthy volunteers) had monocyte mRNA-TLR4 expression (TLR4ex). DGF+ were divided by median of TLR4ex (-0.1034) into 2 groups: low-TLR4 expression (L-TLR4ex) and high-TLR4 expression (H-TLR4ex). RESULTS: We showed that in comparison with DGF-, the DGF+ had much lower TLR4ex, and worse KT function both currently (TLR-day) (serum creatinine [sCr] P = .002; estimated glomerular filtration rate [eGFR] P = .001) and post follow-up (sCr P = .006; eGFR P = .005). The DGF+ with L/H-TLR4ex comparison showed no differences in TLR-day KT function but did show differences in post follow-up (sCr P = .01; eGFR P = .02; ΔeGFR% P = .001). Regression analysis showed an association between recipient age, tacrolimus concentration, and uremic milieu (ie, TLR-day sCr and GFR with TLR4ex). Reverse regression analysis indicated an association of TLR4ex (especially L/H-TLR4ex) with post follow-up parameters of KT function and numeric/qualitative measures of change. CONCLUSION: DGF affects the fate of a graft. Within a several months after transplantation, TLR4ex of peripheral blood mononuclear cells declines in DGF patients. Low LR4ex in patients with DGF+ is associated with poor prognosis for the efficiency of the KT. In patients with DGF+, the proper selection of immunosuppression (tacrolimus dosing) is very important. Higher concentrations of tacrolimus may improve prognosis. The analysis of TLR4ex change may be a useful parameter for the real assessment of immunosuppression efficacy. It is important for transplanted organ function that peripheral blood mononuclear cells effectively leave circulation and remain in the graft.

Pretransplantation Oral Glucose Tolerance Test Can Prevent Posttransplant Diabetes Mellitus After Renal Transplantation: Preliminary Study.

Posttransplant diabetes mellitus (PTDM) adversely affects renal graft and patient survival. Fasting plasma glucose (FPG) alone underestimates diagnosis of glucose metabolism disorders (GMD) detected using the oral glucose tolerance test (OGTT-75). Prediabetes including impaired fasting glucose (IFG): 100 to 125 mg/dL (5.6-6.9 mmol/L) and impaired glucose tolerance (IGT): 140 to 199 mg/dL (7.8-11 mmol/L) 2 hours post 75-g OGTT in the pretransplant period can have a connection with the occurrence of PTDM after renal transplantation (RTx). The aim of our study was to assess the benefit of performing OGTT-75 in dialyzed chronic kidney disease (stage 5) patients on the waiting list for kidney transplantation as a useful tool to prevent PTDM. MATERIALS AND METHODS: Pretransplant glucose testing using OGTT-75 was performed in nondiabetic dialyzed chronic kidney disease patients on the waiting list for renal transplantation in the southwest region of Poland. GMD were diagnosed according to current criteria. Patients with recognized prediabetic stage were recommended a low carbohydrate diet, lifestyle modification, and increased physical activity. In the 12-month posttransplant period we estimated the prevalence of PTDM in the study group based on FPG >126 mg/dL (7 mmol/L) in 2 measurements or random blood glucose >200 mg/dL (11.1 mmol/L). RESULTS: A total of 80 nondiabetic dialysis patients (65 hemodialysis/15 peritoneal dialysis; 47 male/33 female) met initial entry criteria. In pretransplant glucose testing prediabetes was found in 31 out of 80 patients (39%). Among them, 5 patients (6.25%) had combined IGT/IFG, 18 patients (22.5%) had IGT, and 8 patients (10%) had IFG. One year after RTx we recognized PTDM in 14% of all analyzed patients (11/80) and noticed a significant frequency of glucose disorders status change after RTx (P  = .002). CONCLUSION: Our findings suggest early detection of prediabetes using the OGTT-75 test in nondiabetic dialysis patients waiting for RTx to prevent occurrence of PTDM.

Endothelin A Receptors Expressed in Renal Blood Vessels of Renal Transplant Patients Are Connected With Acute Tubular Necrosis or Antibody-Mediated Rejection.

BACKGROUND: The role of non-HLA antibodies named antiendothelin A receptor antibodies is potentially significant but not established. The significance of the endothelin A receptor (ETAR) and its expression in renal biopsy has not been defined. We decided to evaluate the presence and relevance of ETARs in renal transplant biopsy for cause. The aim of our study was to evaluate the immunoreactivity of the ETAR and its significance in patients who had a renal transplant biopsy due to deterioration of transplant function (biopsy for cause) with detailed characterization of staining in small and intermediate arteries of renal transplant biopsies. METHODS: Immunohistochemical expression of ETARs was analyzed in 162 renal transplant biopsies. Microscopic evaluation of ETAR expression (polyclonal antibody) was performed on paraffin sections. ETAR expression was analyzed in renal blood vessels (small and intermediate arteries) based on three-step scale. RESULTS: We analyzed 154 patients who had renal allograft biopsy between 6 days and 24 years (median 597 days) after transplantation. Positive staining of ETAR in small and intermediate arteries was noticed in 9 patients. Among these patients, 4 had early biopsies (<3 months after transplantation), all developed acute tubular necrosis, and 1 developed additionally acute humoral rejection. Further, 4 patients had late biopsy (1-8 years after transplantation) and all developed characteristics of antibody mediated rejection. Lastly, 1 patient had no characteristic changes in the biopsy 4 months after transplantation. Graft loss 1 year after biopsy was higher in patients who were ETAR-positive but statistical significance was not achieved. CONCLUSIONS: The expression of endothelin receptors in renal blood vessels (small and intermediate arteries) seems to be important in diagnosis of damage during acute tubular necrosis and antibody-mediated rejection.

Lowering of Messenger Ribonucleic Acid Toll-Like Receptors 2-4,9 in Peripheral Blood Mononuclear Cells in Kidney Allograft Recipients, Relationships With Immunosuppressive Treatment, and Delayed Graft Function Occurrence.

BACKGROUND: Both tacrolimus (Tac) and cyclosporine (CsA) inhibit control peripheral blood mononuclear cells (PBMC) after stimulation of various Toll-like receptors (TLR) at supra-pharmacological concentrations. Earlier studies demonstrated that 24 hours after kidney transplantation (KT), the expression of the TLR4 messenger RNA (mRNA) in PBMC from patients with subsequent delayed graft function (DGF+) was lower than in patients without DGF (DGF-). An assessment was made of the interaction of immunosuppression with TLR mRNA in PBMC and to verify whether the reduced expression of TLR-2,3,4,9 mRNA in PBMC is permanent in DGF+. METHODS: We investigated mRNA expression of TLR in non-stimulated PBMC. All patients were transplanted more than 1 month before PBMC acquisition. Patients were divided into groups with respect to positive or negative history of delayed graft function (DGF+/-). RESULTS: The expression of TLR2, TLR3, and TLR9 in patients was lower than that in the control group. We found an association of Tac C0 with expression of TLR4 only and CsA dose per 1 kg body weight with TLR2 or up to 6 months after KT with TLR9. Mofetil mycophenolate (MMF)contributed to the change of TLR4 expression in the CsA group but not in the Tac group. TLR3 and TLR9 were nearly equally sensitive to both Tac and CsA, with a decrease of expression with respect to control. DGF+ was associated with variable degree of reduction of TLR2, TLR3, TLR4, and TLR 9 expression. CONCLUSIONS: We showed the importance of immunosuppression and delayed graft function as factors that modify the overall expression of mRNA-TLR PBMC for a period of time after KT. Patients with a history of DGF have chronically decreased expression of mRNA TLR2, TLR3, TLR4, and TLR9. This fact is associated with poorer graft function. Measuring the expression of the TLR in the upper range of therapeutic doses of calcineurin inhibitors and MMF gives the opportunity to assess the strength, effectiveness, and toxicity of immunosuppression.

A significant role for anti-human leukocyte antigen antibodies and antibody-mediated rejection in the biopsy-for-cause population.

The role of anti-human leukocyte antigen (HLA) antibodies and antibody-mediated rejection is well known, but our comprehension and the preventive measures we take seem to be insufficient. One of the major causes of premature renal transplant loss is recepients' immunologic hyperactivity to donors' antigens. Monitoring of humoral alloreactivity gives hope for early diagnosis and adequate therapy. The goal of our analysis was the assessment of the influence of anti-HLA antibodies on the function and survival of transplants. In our study we included 60 consecutive renal transplant recipients who had a renal transplant biopsy-for-cause performed due to insufficiency. Transplant biopsies were performed between the 7th day and 12th year (median, 2 years) after transplantation. Anti-HLA antibodies were present in 20 patients (33%). The patients were divided into 2 groups according the presence of anti-HLA antibodies. In a 12-month observation, 10/20 (50%) patients in the anti-HLA(+) group returned to dialysis in contrast with 7/40 (17.5%; P = .014) in the anti-HLA(-) group. Also, 8/10 (80%) of the anti-HLA(+) patients who lost the transplant had anti-HLA Abs class II and only 2/10 (20%) had anti-HLA Abs class I. Anti-HLA antibodies were specific to a donor (donor-specific antibodies [DSA]) in 8/10 (80%) of the patients who lost the transplant. Anti-HLA antibodies appeared de novo in 50% of patients who lost the transplant. Nonadherence was suspected in 50% of patients. Acute humoral rejection occurred in 1 patient. Also, 8/10 (90%) developed chronic active humoral rejection. Our study revealed that graft loss in the renal transplant biopsy-for-cause population with the presence of anti-HLA Abs during a 12-month observation reached 50%. Nonadherence in these patients was very high and amounted to 50%. Monitoring of renal transplant recipients and individualization of therapy considering humoral activity should prolong renal graft survival.

Non-HLA antibodies: angiotensin II type 1 receptor (anti-AT1R) and endothelin-1 type A receptor (anti-ETAR) are associated with renal allograft injury and graft loss.

INTRODUCTION: Non-HLA antibodies specific for angiotensin II type 1 receptor (anti-AT1R) and endothelin-1 type A receptor (anti-ETAR) of vascular cells activate signaling pathways leading to cell proliferation and vascular injury. The aim of this study was to evaluate the impact of non-HLA antibodies on kidney allograft morphology and function in patients who underwent a kidney biopsy due to renal function impairment. PATIENTS AND METHODS: The study included 65 consecutive renal transplant patients who were evaluated for the presence of non-HLA and anti-HLA antibodies at the time of transplant biopsy. Results of pre-transplant CDC cross-match were negative. A kidney allograft biopsy was performed between 6 days and 13 years (42 ± 49 months) after transplantation, and the diagnosis was made on the basis of the Banff criteria. The level >9 U/L of anti-AT1R and anti-ETAR antibodies was considered high. RESULTS: A high level of non-HLA antibodies (anti-AT1R and/or anti-ETAR) was found in 7 (10.7%) of 65 patients at the time of biopsy. Graft loss in the non-HLA-positive patients was significantly higher (71% in non-HLA-positive cases after 7.8 ± 2.6 months vs 11% after 6 months in non-HLA-negative cases [P = .00099]). In these non-HLA-positive patients, the mean anti-AT1R level was 15.3 ± 9.4 U/L and the mean anti-ETAR level was 13.8 ± 8.6 U/L. In only 2 of these patients were anti-HLA antibodies additionally detected: anti-class I in 1 and anti-class II in both patients. The mean serum creatinine level was 2.34 ± 0.6 mg/dL at the time of biopsy. Results of an early biopsy revealed acute vascular rejection (Banff grade IIB). Chronic allograft injury was found (grading cg1-3, cv1-2, ci1-2, ct1-2) in the remaining 6 patients. C4d was present in 3 of 7 patients. CONCLUSIONS: High levels of anti-AT1R and/or anti-ETAR antibodies were associated with morphological and functional allograft injury and graft loss in these study patients. Non-HLA antibodies can be helpful in assessing the risk of graft failure.

Increased plasma matrix metalloproteinase-2 (MMP-2), tissue inhibitor of proteinase-1 (TIMP-1), TIMP-2, and urine MMP-2 concentrations correlate with proteinuria in renal transplant recipients.

BACKGROUND: The most frequent cause of kidney allograft loss is chronic allograft injury, often with proteinuria as the clinical feature. Occurrence of proteinuria late after kidney transplantation is associated with worse graft function and patient survival. AIM: The aim of the study was to assess plasma and urine matrix metalloproteinases (MMP-2 and MMP-9) and tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) in proteinuric renal transplant recipients (RTRs). The factors were determined by enzyme-linked immunosorbent assay in 150 RTRs (51 women and 99 men), aged 49.2 ± 11.5 years, at mean 73.4 ± 41.2 months after kidney transplantation (range: 12 to 240 months). RESULTS: Proteinuric RTRs compared with non-proteinuric RTRs had higher median plasma MMP-2 (P = .012), TIMP-1 (P = .0003), and TIMP-2 (P = .0021) concentrations, as well as higher urine MMP-2 (P < .0001) excretion. The presence of proteinuria had no impact on plasma MMP-9 and urine MMP-9, TIMP-1, and TIMP-2. Proteinuria and estimated daily proteinuria (uPr:uCr) correlated positively with plasma MMP-2 (rs = 0.226, P = .0054 and rs = 0.241, P = .003), TIMP-1 (rs = 0.305, P = .00015 and rs = 0.323, P = .000055), TIMP-2 (rs = 0.273, P = .0007 and rs = 0.269, P = .001) and urine MMP-2 (rs = 0.464, P < .0001 and rs = 0.487, P < .0001), respectively. Proteinuric RTRs had impaired graft function with higher median serum creatinine concentrations (1.91 [1.60-2.43] mg/dL versus 1.41 [1.20-1.65] mg/dL, P < .00001) and lower estimated glomerular filtration rate (36 [28-45] mL/min/1.73 m(2) versus 53 [43-61] mL/min/1.73 m(2), P < .00001) than RTRs without proteinuria. CONCLUSIONS: Our research revealed that in RTRs, proteinuria was significantly associated with increased concentrations of enzymes involved in extracellular matrix (ECM) degradation: plasma MMP-2, TIMP-1, TIMP-2, and urine MMP-2. Findings strongly emphasize increased plasma TIMPs in proteinuric RTRs that inhibit degradation of ECM by MMPs and favor excessive deposition of ECM proteins.

Advanced age of renal transplant recipients correlates with increased plasma concentrations of interleukin-6, chemokine ligand 2 (CCL2), and matrix metalloproteinase 2, and urine concentrations of CCL2 and tissue inhibitor of metalloproteinase 1.

BACKGROUND: Advanced age of renal transplant recipients (RTRs) has a negative impact on kidney allograft survival through impaired extracellular matrix degradation by the matrix metalloproteinases/tissue inhibitors of metalloproteinases (MMPs/TIMPs) system. Moreover, older RTRs are at risk of smoldering inflammation, known as inflammaging. AIM: The aim of the study was to assess the impact of a RTR's age on plasma and urine concentrations of interleukin 6 (IL-6), chemokine ligand 2 (CCL2), and the MMPs/TIMPs system. MATERIAL AND METHODS: One hundred fifty adult RTRs (8.7% ≥ 65 years) and 37 adult healthy volunteers (10.8% ≥ 65 years) were enrolled in the study. The studied factors (IL-6, CCL2, MMP-2, MMP-9, TIMP-1 and TIMP-2) were quantified in plasma and urine with enzyme-linked immunosorbent assay. The Mann-Whitney U test and Spearman's (rs) rank correlation were applied, and differences with a P < .05 were considered statistically significant. RESULTS: There was a weak but significant positive correlation between increasing RTR's age and plasma IL-6 (rs = 0.18, P = .028), CCL2 (rs = 0.27, P = .001), and MMP-2 (rs = 0.20, P = .017), as well as urine CCL2 (rs = 0.16, P = 0.050) and TIMP-1 (rs = 0.20, P = .014) concentrations. CONCLUSIONS: Advancing age of RTRs correlates with increasing plasma IL-6 and CCL2 concentrations, reflecting smoldering inflammation (known as inflammaging) and alterations in MMPs/TIMPs profiles, especially with increased plasma MMP-2 and urine TIMP-1 concentrations.

Evolution of bone disease at 2 years after transplantation: a single-center study.

Posttransplant bone disease is caused by renal osteodystrophy. We sought to examine bone mineral density (BMD) among 90 renal allograft recipients of mean age 42.7 +/- 11.4 years to identify factors preventing bone loss at 2 years posttransplant. Subjects treated with cyclosporine or tacrolimus plus azathioprine/MMF and prednisone underwent BMD estimates of the lumbar spine (LS) and of the proximal femur using dual energy x-ray absorptiometry (DEXA) at 3 months and every 6 months for 2 years. We assayed markers of bone remodeling: intact parathyroid hormone (iPTH), calcitriol, osteocalcin, and carboxyterminal telopeptide of type I collagen on day 3, as well as month 1 and every 6 months after transplantation. At the initial measurement, we observed osteopenia (OSP) among 35% in the LS and 52% in the femur: there was osteoporosis in 8.3%. The prevalence of OSP increased during the first year, thereafter decreasing to the initial value, but the rate of osteoporosis did not change significantly (8.3% vs 6.0%). BMD and Z-score decreased during the first and increased in the second year; 27% of patients regained initial values and 38% higher ones. BMD gains in the LS and femur were observed among subjects with higher calcitriol levels during the first 6 months (P < .01), higher osteocalcin (P < .05), higher estimated glomerular filtration rate during 1-24 months and in the tacrolimus group. Improvement of LS BMD occurred in younger patients (38 vs 46 years; P < .027); BMD gain in the femur correlated with higher levels of iPTH from 1-12 months (P < .01). The tacrolimus group showed higher Z-scores in the LS and femur at 24 months (P < .05). Two years after transplantation >60% of recipients showed stabilization or gain in bone mass. A sufficient calcitriol level in the early transplant period, an adequate iPTH, good renal function, and tacrolimus therapy prevented BMD disease progression.

The abnormal superficial radial artery does not restrict the successful creation of hemodialysis forearm arteriovenous fistula.

Anatomical variations of the radial artery are of clinical importance in end-stage renal disease patients awaiting creation of native arteriovenous fistula for hemodialysis. As radial-cephalic direct wrist fistula is a vascular access of choice, atypical localization of the distal part of the radial artery may lead to the false assumption of severe atherosclerotic lesions and prevent creation of such an access, despite good vessel conditions and convenient surgical approach. We present 7 patients with radial artery variations. In 5 patients with superficial radial artery, radial-cephalic direct wrist access was created. One patient, due to an anomaly misdiagnosis, had radial-cephalic fistula created on the contra lateral wrist. In the patient with hypoplastic radial artery brachial-basilic upper arm transposition was created.

Regression of Kaposi's sarcoma in renal graft recipients after conversion to sirolimus treatment.

Kaposi's sarcoma (KS) is a rare complication of renal transplantation in Poland (in our center 2 of 1000 patients). Neovascularization (typical for KS) is promoted by KS-related vascular endothelial growth factor (t-r-VEGF). Sirolimus may reduce t-r-VEGF synthesis and inhibit PI3K-p70S6 kinase of endothelial cells. Two men, 58 and 51 years old, were transplanted in 2002. Initial immunosuppression consisted of cyclosporine, azathioprine, and prednisone. In the second patient, at the week 8 the immunosuppression was switched to tacrolimus and mycophenolate mophetil. KS symptoms appeared on hard palate and skin in month 7 in both patients. In the first patient, the X-ray showed enlargement of mediastinal lymph nodes and diffuse interstitial infiltrates with nodular changes in both lungs. Serum creatinine of the first patient was increased from 1.6 to 1.9 mg/dL, while in the second it remained stable (approximately 2.0 mg/dL). Since confirmation of KS immunosuppression has been minimized in both patients; all drugs except prednisone were withdrawn, and sirolimus was introduced (1-2 mg/24 hours blood level 5-8 ng/mL). Within a month the progression of lung and skin disease ceased, and patients' conditions began to improve with lung opacities regressing, the biggest skin lesions diminishing and smaller ones disappearing. Within 1 year renal function improved. Our observation suggests that sirolimus-based immunosuppression proffers the possibility of KS regression with concomitant renal function preservation among renal graft recipients. It is difficult to ascertain whether KS regression may be attributed to sirolimus treatment or to the reduced overall immunosuppression.

Influence of vitamin D receptor gene polymorphisms on secondary hyperparathyroidism and bone density after kidney transplantation.

Secondary hyperparathyroidism and immunosuppressive treatments are the most important pathogenetic factors for bone disease after kidney transplantation. The aim of study was to compare the influence of vitamin D receptor (VDR) genotype on the PTH level and bone mineral density (BMD) in 67 patients, including 45 immunosuppressed with cyclosporine (CsA) and 22 with tacrolimus (Tac) versus 147 healthy volunteers. Two VDR polymorphisms: BsmI and FokI were assayed with RFLP-PCR. Scantibodies were utilized to evaluate 1-84 PTH. BMD was measured by DEXA. Hormone levels were measured on the third day and sixth month after transplantation. BMD was examined at the third and ninth month. The distribution of FokI genotype differed, but the BsmI genotypes did not differ between the transplant patients and the control group. All transplanted patients showed an elevated tPTH at the first examination. The highest PTH values, which were observed in bb genotype, significantly decreased after the transplant procedure. Patients with the FF genotype who were treated with CsA showed higher levels of tPTH than those with the Ff genotype. At 6 months, a decrease in tPTH occurred in both the CsA and the Tac patients. A low BMD at the third month was more frequent among patients of the BB genotype treated with CsA. The Z-score remained low at the third month and at the ninth month. In conclusion, kidney graft recipients show overrepresentation of the Ff genotype. Our preliminary data suggest that the bb genotype exhibits a protective effect on bone loss after renal transplantation.

Mycophenolate mofetil severely depresses antibody response to CMV infection in early posttransplant period.

Estimation of anti-CMV-IgG and anti-CMV-IgM is considered a relatively inexpensive screening tool of CMV status. The aim of study was to estimate how the immunosuppressive protocol influence serum anti-CMV IgG and IgM concentration in renal graft recipients and to estimate the adequacy of anti-CMV-IgG concentration and anti-CMV-IgM index as screening parameters of active CMV disease in patients receiving different immunosuppression. The study group consisted of 33 patients with clinical signs of CMV disease who received one of three types of immunosuppression: (1) azathioprine (Aza) + cyclosporine (CyA) + prednisone (Pr), 20 patients; (2) mycophenolate mofetil (MMF) + CyA + Pr, eight patients; tacrolimus (Tac) + MMF, five patients. Patients were enrolled when the pp65-antigen (pp65) of PBL was positive within 1 to 5 months after transplant (75 patients tested). The IgM-i in the Aza + CyA + Pr group was higher than in MMF + CyA + Pr group (2.73 + 1.8 vs 1.08 +/- 1.07, P =.021). The IgM-i in the Aza + CyA + Pr group was higher than in Tac + MMF (2.73 +/- 1.8 vs 0.78 +/- 0.69; P =.014). There was no difference in IgM-i between MMF + CyA + Pr and Tac + MMF. There was no difference in relative increase of IgG-c among all groups but there was a difference in relative increase of IgM-i between Aza + CyA + Pr and MMF + CyA + Pr groups (6.7 +/- 9.4 vs 2.3 +/- 5.9; P =.007) and between Aza + CyA + Pr and MMF + Tac groups (6.7 +/- 9.4 vs 0.6 +/- 0.54; P =.003). Immunosuppressive protocols including MMF exert an inhibitory influence on B-cell response and synthesis of anti-CMV-IgM. It makes the anti-CMV-IgM index an inadequate rough screening diagnostic parameter of active CMV disease.

[Therapeutic use of potassium citrate]. / Terapeutyczne zastosowania cytrynianu potasu.

Therapeutic indications of potassium citrate include: 1. Oxaluric renal stone disease and some cases of uric acid stone disease. Prevention of stone formation in patients with renal polycystic disease. Prevention of stone relapse after ESWL or lithotomy; 2. Distal renal tubular acidosis complicated by hypercalciuria, mainly in children. 3. Renal hypercalciuria and hyperoxaluria. 4. Prevention of renal complications at the time of glaucoma treatment with acetazolamide. 5. Potassium supplementation during treatment of hypertension. Potassium citrate is usually contraindicated in the case of: 1. Urinary tract infection. 2. Struvite renal stone disease. 3. Hyperpotassemia and advanced chronic renal failure. 4. Peptic ulcer or gastritis. 5. Gastrointestinal bleeding. 6. Disorders of coagulation, crural varices. 7. Metabolic alkalosis. Potassium citrate, when used at therapeutic doses, is to be considered as quite safe. The average daily dose even if admitted as a single dose day engages 60-75% of free renal capacity for potassium excretion. Physiologic and therapeutic citrate concentration in urine exceeds much those available for other inhibitors. The therapeutic dose does not induce any significant changes in any biochemical or endocrine parameter of blood except mild transient metabolic alkalosis. The decrease of urine calcium and increase in oxalate calcium phosphate excretion is observed. In hypo-cytriaturic patients the response to therapeutic dose of citrate is smaller. One-year remission of stone disease is observed in 70-75% cases.

[Antiphospholipid antibody syndrome in systemic lupus erythematosus]. / Zespól prezeciwcial przeciwfosfolipidowych w toczniu trzewnym.

Various hemostatic abnormalities that can be met in the course of apparently unrelated diseases are caused by antiphospholipid antibodies (APA). Nearly on half of the population with antibodies detectable in serum suffer from systemic lupus erythematosus (SLE) or the disease will be diagnosed in the future. The supposition considering that APA do not bind phospholipids directly becomes popular recently. They bind serum beta 2-Glycoprotein. The APA-beta 2 GIP complexes speed up prothrombin activation and make beta 2 GIP less available for serum C- and S-protein transformation. APA are a heterogenous population of antibodies. Postinfectious APA differ from those found in autoimmune diseases. Thrombotic events caused by APA are treated according to general principles. Steroid therapy is essential in treatment programme of SLE with APA. In severe cases it is supplemented by intravenous cyclophosphamide. Plasmapheresis and intravenous immunoglobulins are of limited usefulness. In severe resistant thrombocytopenia one can try to introduce Danazol carefully.

Patch-clamp study on T-lymphocyte potassium conductance in patients with chronic renal failure.

Using the patch-clamp technique, we studied the differences in whole-cell potassium conductance (g(K)+) in T lymphocytes (TL) from three groups of patients suffering from renal failure: not dialyzed patients, dialyzed patients, and dialyzed patients treated with human recombinant erythropoietin (rHuEPO). The differences in g(K+) values in the group of not dialyzed patients in comparison with controls was not significant (p > 0.05). In the group of dialyzed patients, after roughly 6 years of the hemodialysis therapy, the g(K+) value was significantly higher than in controls. In dialyzed patients treated with rHuEPO, g(K+) value was significantly lower in comparison with control. Moreover, in dialyzed patients treated with rHuEPO, the time duration of dialysis therapy did not significantly affect the TL whole-cell conductance. We conclude that the g(K+) is changed in TL in renal failure patients and that the time duration of hemodialysis therapy as well as the use of rHuEPO affect the g(K+) value. Possible mechanisms underlying the observed changes in g(K+) values, as well as medical implications of obtained results are discussed.

[Outline of immune deficiency pathogenesis in patients with chronic renal failure]. / Zarys patogenezy niedoboru immunologicznego u chorych na przewlekla niewydolnosc nerek.

Up to day the pathogenesis of immune deficiency in chronic renal failure have not been clearly elucidated. There is no agreement where is situated the primary disturbance that makes that category of patients more susceptible to infections and neoplasms. The views presented in this paper seem to shift the balance toward multifactor theory. Possible influence of many biochemical abnormalities and effect of renal replacement therapies on main elements of immune system are discussed.